Spatially resolved transcriptomic profiling of ovarian aging in mice DOI Creative Commons
Jennifer E. Russ,

Mary E. Haywood,

Sydney L. Lane

et al.

iScience, Journal Year: 2022, Volume and Issue: 25(8), P. 104819 - 104819

Published: Aug. 1, 2022

Ovarian aging precedes that of any other mammalian organ and is the primary cause female age-related infertility. The biological mechanisms responsible for ovarian remain unclear. Previous studies have been limited by their use bulk RNA-sequencing, which masks dynamic heterogeneous nature ovary. In this study, we spatially resolved transcriptomic landscape ovaries from young aged outbred mice. total, defined eight main cell populations, all were characterized significant changes between samples. Further sub-cluster analysis revealed separate transcriptomes distinct granulosa populations found in versus mice, addition to an oocyte population completely absent mouse ovaries. This study provides a new perspective on using spatial transcriptomics achieve deeper understanding localization cell-population-specific underlying fertility decline.

Language: Английский

Ovarian microenvironment: challenges and opportunities in protecting against chemotherapy-associated ovarian damage DOI Creative Commons

Yican Guo,

Liru Xue,

Weicheng Tang

et al.

Human Reproduction Update, Journal Year: 2024, Volume and Issue: 30(5), P. 614 - 647

Published: June 28, 2024

Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance hormone levels, reduced or lost fertility, an increased risk early menopause. Previous studies have often focused on direct chemotherapeutic drugs follicles, such as DNA damage-mediated apoptotic death primordial follicle burnout. Emerging evidence has revealed imbalance microenvironment during chemotherapy. The provides nutritional support transportation signals stimulate growth development ovulation, corpus luteum formation. close interaction between follicles determine function. Therefore, designing novel precise strategies manipulate may be a new strategy protect function

Language: Английский

Citations

15

Ovarian aging: energy metabolism of oocytes DOI Creative Commons
Shenglan Bao, Tailang Yin,

Su Liu

et al.

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 31, 2024

Abstract In women who are getting older, the quantity and quality of their follicles or oocytes decline. This is characterized by decreased ovarian reserve function (DOR), fewer remaining oocytes, lower oocytes. As more choose to delay childbirth, decline in fertility associated with age has become a significant concern for modern women. The oocyte key indicator aging. Many studies suggest that age-related changes energy metabolism may impact quality. Changes affect adenosine 5'-triphosphate (ATP) production, but how related products proteins influence remains largely unknown. review focuses on aging its potential quality, as well therapeutic strategies partially metabolism. research aims enhance our understanding metabolism, identification biomarkers treatment methods.

Language: Английский

Citations

14

The maintenance of oocytes in the mammalian ovary involves extreme protein longevity DOI Creative Commons
Katarina Harasimov, Rebecca L. Gorry, Luisa M. Welp

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(7), P. 1124 - 1138

Published: June 20, 2024

Abstract Women are born with all of their oocytes. The oocyte proteome must be maintained minimal damage throughout the woman’s reproductive life, and hence for decades. Here we report that ovarian proteostasis involves extreme protein longevity. Mouse ovaries had more extremely long-lived proteins than other tissues, including brain. These diverse functions, in mitochondria, cytoskeleton, chromatin proteostasis. stable resided not only oocytes but also somatic cells. Our data suggest mammals increase longevity enhance by chaperones cellular antioxidants to maintain female germline long periods. Indeed, aggregation did age proteasome activity decay. However, increasing cannot fully block senescence. Large-scale profiling ~8,890 revealed a decline many network aging ovary, accompanied massive remodeling, which eventually leads fertility decline.

Language: Английский

Citations

14

Characterization of the human fetal gonad and reproductive tract by single-cell transcriptomics DOI Creative Commons
Jasin Taelman, Sylwia Czukiewska, Ioannis Moustakas

et al.

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(4), P. 529 - 544.e5

Published: Jan. 30, 2024

During human fetal development, sex differentiation occurs not only in the gonads but also adjacent developing reproductive tract. However, while cellular composition of male and female is well described, that tract remains poorly characterized. Here, we performed single-cell transcriptomics on together with from first second trimesters, highlighting morphological molecular changes during differentiation. We validated different cell populations compared signatures between as sexes, to identify conserved sex-specific features. Together, our study provides insights into gonadogenesis development beyond gonads.

Language: Английский

Citations

10

Direct male development in chromosomally ZZ zebrafish DOI Creative Commons
Catherine Wilson,

Peter Batzel,

John H. Postlethwait

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: March 11, 2024

The genetics of sex determination varies across taxa, sometimes even within a species. Major domesticated strains zebrafish ( Danio rerio ), including AB and TU, lack strong genetic determining locus, but more recently derived from nature, like Nadia (NA), possess ZZ male/ZW female chromosomal sex-determination system. fish pass through juvenile ovary stage, forming oocytes that survive in become females die males. To understand mechanisms gonad development NA zebrafish, we studied histology single cell transcriptomics developing ZW fish. developed by 22 days post-fertilization (dpf) directly formed testes, avoiding phase. Gonads some WW fish, however, died as the became testis, mimicking suggesting gynogenetically strain is chromosomally WW. Single-cell RNA-seq 19dpf gonads showed similar types germ cells, precursors gonadal support steroidogenic interstitial/stromal immune consistent with bipotential gonad. In contrast, scRNA-seq 30dpf revealed cells had transcriptomes characteristic testicular Sertoli, Leydig, while granulosa theca oocytes. Hematopoietic vascular were both genotypes. These results show initially develop gonad; factor on W chromosome, or fewer than two Z chromosomes, essential to initiate oocyte development; without factor, doses, into testes passing stage. Sex TU mimics loss chromosome during domestication. Genetic analysis will facilitate our understanding evolution mechanisms.

Language: Английский

Citations

9

Oncogenic Pathways and Targeted Therapies in Ovarian Cancer DOI Creative Commons

Carolina Lliberos,

Gary Richardson, Antonella Papa

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(5), P. 585 - 585

Published: May 15, 2024

Epithelial ovarian cancer (EOC) is one of the most aggressive forms gynaecological malignancies. Survival rates for women diagnosed with OC remain poor as patients are advanced disease. Debulking surgery and platinum-based therapies current mainstay treatment. However, despite achieving initial remission, a significant portion will relapse because innate acquired resistance, at which point disease considered incurable. In view this, novel detection strategies therapeutic approaches needed to improve outcomes survival patients. this review, we summarize our knowledge genetic landscape molecular pathways underpinning its many subtypes. By examining explored in preclinical clinical settings, highlight importance decoding how single convergent alterations co-exist drive progression resistance treatments. We also propose that core signalling such PI3K MAPK play critical roles origin diverse subtypes can become new targets combination known DNA damage repair development tailored more effective anti-cancer

Language: Английский

Citations

9

Molecular Mechanisms of Laparoscopic Ovarian Drilling and Its Therapeutic Effects in Polycystic Ovary Syndrome DOI Open Access
Kok‐Min Seow,

Yi-Wen Chang,

Kuo-Hu Chen

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 8147 - 8147

Published: Oct. 31, 2020

Polycystic ovary syndrome (PCOS) is a common endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and multiple small subcapsular cystic follicles in the during ultrasonography, affects 5–10% of women reproductive age. PCOS frequently associated with insulin resistance (IR) accompanied compensatory hyperinsulinemia and, therefore, presents an increased risk type 2 diabetes mellitus (DM). The pathophysiology unclear, many hypotheses have been proposed. Among these hypotheses, IR hyperandrogenism may be two key factors. first line treatment includes lifestyle changes body weight reduction. Achieving 5–15% reduction improve PCOS-associated hormonal abnormalities. For who desire pregnancy, clomiphene citrate (CC) front-line for ovulation induction. Twenty five percent fail to ovulate spontaneously after three cycles CC treatment, which called CC-resistant PCOS. women, there are strategies rate, including medical surgical approaches. various approaches, one particular method, laparoscopic ovarian drilling (LOD), has proposed as alternative treatment. LOD results overall spontaneous rate 30–90% final pregnancy rates 13–88%. These benefits more significant Although intra- post-operative complications sequelae always important, we believe that better understanding pathophysiological and/or molecular mechanisms provide rationale this procedure. LOD, mediated mainly thermal effects, produces series morphological biochemical changes. include formation artificial holes very thick cortical wall, loosening dense hard destruction subsequently decreased amount theca granulosa cells, stromal tissue subsequent development transient but purulent acute inflammatory reactions initiate immune response, continuing leakage or drainage “toxic” follicular fluid immature growth-ceased pre-antral follicles. All factors contribute decreasing local systemic androgen levels, following apoptosis process atresia; re-starting normal recruitment, development, maturation, finally, normalization “hypothalamus–pituitary–ovary” axis ovulation. detailed systematic comprehensively reviewed current article.

Language: Английский

Citations

53

Single-cell sequencing reveals suppressive transcriptional programs regulated by MIS/AMH in neonatal ovaries DOI Creative Commons
Marie-Charlotte Meinsohn, Hatice D. Saatcioglu, Lina Wei

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(20)

Published: May 12, 2021

Müllerian inhibiting substance (MIS/AMH), produced by granulosa cells of growing follicles, is an important regulator folliculogenesis and follicle development. Treatment with exogenous MIS in mice suppresses development prevents ovulation. To investigate the mechanisms which inhibits development, we performed single-cell RNA sequencing whole neonatal ovaries treated at birth analyzed postnatal day 6, coinciding first wave growth. We identified distinct transcriptional signatures associated responses ovarian cell types. treatment inhibited proliferation granulosa, surface epithelial, stromal types ovary elicited a unique signature quiescence cells. In addition to decreasing number preantral found that uncoupled maturation germ conclusion, suppressed proliferation, imposing quiescent state, preventing differentiation.

Language: Английский

Citations

53

Long-term treatment of Nicotinamide mononucleotide improved age-related diminished ovary reserve through enhancing the mitophagy level of granulosa cells in mice DOI
Pan Huang, Yan Zhou, Weihong Tang

et al.

The Journal of Nutritional Biochemistry, Journal Year: 2021, Volume and Issue: 101, P. 108911 - 108911

Published: Nov. 19, 2021

Language: Английский

Citations

43

CD38 regulates ovarian function and fecundity via NAD+ metabolism DOI Creative Commons
Rosalba Perrone,

Prasanna Vadhana Ashok Kumaar,

Lauren Haky

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(10), P. 107949 - 107949

Published: Sept. 16, 2023

Language: Английский

Citations

22